Essential Fatty acids, their funtions, sources and related risks Eicosanoids and their role in body Cox enzymes and NSAIDs mechanism

1. Biochemistry of Lipids
BY
DR. SAMINA

3. Learning Objectives
By the end of this lecture students must be
able to
 Describe functions and deficiency effects
of essential fatty acids
 Define Eicosaoinds
 Describe functions and clinical
importance of prostaglandins

4. Fatty-acid Nomenclature…Isomerism
 If H-atoms / acyl group present on same side..
Cis . If on opposite direction ..trans fatty acids
Every double bond… produce bend in structure

5. Fatty Acids in the Human body
 Palmitic acid (16) and stearic acid (18) are most common
fatty acids
 Essential fatty acids: polyunsaturated fatty acids that the
body can not make
Important: linoleic and linolenic acids
 Linoleic (18:2Δ 9,12) ω6
 Linolenic (18:3 Δ 9,12,15) ω3
 Arachidonic (20:4 Δ 5,8,11,14) ω6 (Optional)

6. Dietary Sources of EFAs
 Fish, flaxseed (linseed), and flaxseed oil, chiaseed, olive oil, soya
oil, canola oil, pumpkin seeds, sunflower seeds, leafy vegetables,
and walnuts; but most of these food sources are poor sources of
EFA's.
 Flaxseeds are the best source of ω-3 EFA, next is chiaseed, lastly
hempseed; sunflower and starflower seeds are the best sources of
ω-6 EFA.
chiaseed flaxseed (linseed
soya oil
canola oil

7. Function of EFAs
 Formation of healthy cell membranes
 Proper development and functioning of the brain,
nervous system and gonads
 Production of hormone-like substances called
Eicosanoids
 Clotting time is affected by EFA
 Responsible for regulating blood pressure, blood
viscosity, vasoconstriction, immune & inflammatory
responses.

8. Essential Fatty Acid Deficiency /Side Effects
 Hemorrhagic/skin dermatitis
 Skin atrophy
 Scaly dermatitis
 Fatty liver
 Weakness
 Impaired vision
 Tingling sensations
 Mood swings
 Edema
 Phrynoderma/ toad like skin
 high blood pressure
 high triglycerides
 hemorrhagic folliculitis
 hemotologic disturbances (e.g:
sticky platelets)
 immune and mental
deficiencies
 impaired growth
Dandruff like
scaly dermatitis

9. Dermatitis,
Atopic (allergic/ hypersensitivity) in an Infant

10. WHO ARE AT RISK FOR DEFICIENCY?
• Cystic Fibrosis
• Low Birth Weight Infants
• Premature infants
• Severely malnourished patients
• Patients on Long-term MCT (medium
chain TG)as fat source
• Patients with fat mal-absorption
• Multisystem neuronal degradation
• Cirrhosis and alcoholism

11. Eicosanoids
 Eicosanoids Derived from arachidonate or arachidonic acid
Comparise…Prostanoids, Leukotrienes & Lipoxins
 Prostanoids include..Prostaglandins (PGs), Prstacyclins & Thromboxanes
 Prostaglandins---- Local hormones
 Prostacyclins ----- reduce platelet stickiness and cause dilation of the blood
vessels.
 Thromboxanes (TX) -- vasoconstrictor, potent hypertensive agent &
facilitates platelet aggregation
 Leukotrienes (LT) – triggers contractions in the smooth muscles lining the
trachea. Their over- production is a major cause of inflammation in asthma
 Lipoxins.. They have a number of immunomodulatory and anti-inflammatory
actions. whose appearance in inflammation signals the resolution of
inflammation.

12. Prostaglandins (PGs)
PGs, serve as local chemical messengers
---Arachidonic acid is precursor
Almost in every tissue of body (except,
RBCs)
Not stored in the body , Mostly Act
through 2nd messenger cAMP

13. Eicosanoids

14. Prostaglandins
 Lowers blood pressure ---Vasodilator PGs, i.e. PGA and prostaglandin E
(PGE2).
 Inhibition of gastric secretion ----Protection of stomach lining. (PGE1, A1)
 Use for the treatment of Gastric ulcers, Bronchial asthma
 Mediation of inflammatory responses
 Regulation by steroids ---- glucocorticoids
inhibit phospholipase A2 (require for eicosanoid synthesis).. Regulatory action
 Inhibition of hormone sensitive lipases…decrease lipolysis
 Decrease immunological response… effect on T & B lymphocytes
 Over production --- Pain, inflammation, fever, nausea or vomiting.
 Asprin, Brufen, Diclofenac or anti inflammatory agents--- prevent
conversion of Arachidonic Acid into PGs.

15. Clinical uses… synthetic PGs
 To induce childbirth or abortion (PGE2 or PGF2)
 To prevent closure of patent ductus arteriosus in newborns with
particular cyanotic heart defects (PGE1)
 To prevent and treat peptic ulcers (PGE)
 As a vasodilator in ischemia of a limb
 In pulmonary hypertension
 In treatment of glaucoma
 As an ingredient in eyelash and eyebrow growth beauty products due
to side effects associated with increased hair growth
Patent ductus arteriosus (PDA) is a condition in
which the ductus arteriosus does not close. After
the infant is born and the lungs fill with air, the
ductus arteriosus is no longer needed. It usually
closes in a couple of days after birth.
Cyanotic heart disease is a heart defect,
present at birth (congenital), that results in
low blood oxygen levels.
Glaucoma is an eye disease in which the optic nerve is
damaged in a characteristic pattern. This can permanently
damage vision in the affected eye(s) and lead to blindness if
left untreated. It is normally associated with increased fluid
pressure in the eye (aqueous humour).

16. Effects of Aspirin & other Pain Killers.. NSAIDs
 Aspirin blocks an enzyme called cyclooxygenase1 and 2,
which is involved with the ring closure and addition of
oxygen to arachidonic acid converting to prostaglandins.
 By inhibiting or blocking this enzyme, the synthesis of
prostaglandins is blocked, which in turn relives some of the
effects of pain and fever.

17. Key Points
 Dietary Essential or non essential fatty acids are Clinically
important
 Arachidonic acid is the precursor of eicosanoids
 Prostaglandins have variety of functions
 NSAIDs block production of PGs by inhibiting cox-1 and cox-II
enzymes

18. Next topic of Discussion
 Properties of fatty acids
• Take Home Activity
Clinical significance of Eicosanoids

20. • https://www.youtube.com/watch?v=BYbyhePh78I
• https://www.youtube.com/watch?v=Jc7H1W2lKK4
• https://www.youtube.com/watch?v=lHuu28diC_I
Animations for better understanding

22. There are currently ten known prostaglandin receptors on various cell types. These receptors are
termed DP1-2, EP1-4, FP, IP1-2, and TP, corresponding to the receptor that ligates the
corresponding prostaglandin (e.g., DP1-2 receptors bind to PGD2).
The diversity of receptors means that prostaglandins act on an array of cells & have a wide variety
of effects Type Receptor Function
PGI2 IP
•vasodilation
•inhibit platelet aggregation
•bronchodilation
PGE2
EP1
•bronchoconstriction
•GI tract smooth muscle contraction
EP2
•bronchodilation
•GI tract smooth muscle relaxation
•vasodilation
EP3
•↓ gastric acid secretion
•↑ gastric mucus secretion
•uterus contraction (when pregnant)
•GI tract smooth muscle contraction
•lipolysis inhibition
•↑ autonomic neurotransmitters
•↑ platelet response to their agonists and ↑ atherothrombosis in vivo
Unspecified
•hyperalgesia[7]
•pyrogenic
PGF2α FP
•uterus contraction
•bronchoconstriction
Deep diving about PGs